LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).
Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.
Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.
Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.
Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).
Patients and treatment
The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.
The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.
The GAD-M regimen consisted of:
- Gemcitabine given at 1000 mg/m2 via intravenous drip on days 1 and 8
- PEG-asparaginase given at 2500 U/m2 intramuscularly on day 1
- Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
- Methotrexate given at 3000 mg/m2 via continuous, 12-hour infusion on day 1.
The regimen was repeated every 3 weeks.
For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.
Response and survival
The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.
In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.
In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.
At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.
For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.
Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).
Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).
The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.